Substantial progress has been made in several of the projects and the plan is to develop these further along the lines of the original grant proposal. 1. Preliminary results suggesting the in vivo importance of penicillin tolerance in a rabbit heart infection model had been obtained with S. sanguis. We are planning detailed characterization of the physical fate of tolerant and lysis-prone bacteria within the infected animal. 2. Using a penicillin labeled with very high specific radioactivity isotope we are completing a study of the cellular access, turn-over rates and biosynthesis of the penicillin binding proteins (PBP) of group A stretptococci. 3. Two phenomena suggesting cooperation between immune factors and penicillin have been observed. Penicillin pretreatment of S. sanguis sensitized these bacteria to the bactericidal and lytic effects of exogenous lysozymes; and similar treatment of group B streptococci made these cells sensitized to the bactericidal effect of human PMN. 4. We have completed the characterization of the PBPs in the multiply drug resistant (South African) strains of pneumococci. Multiple and culmulative changes in two of the three major groups of PBPs were noted. We are planning experiments to identify the enzymatic activities catalyzed by these proteins.